Azithromycin exposure induces transient microbial composition shifts and decreases the airway microbiota resilience from PM2.5 stress in healthy adults: a randomized, double-blind, placebo-controlled trial

Abstract

Background: Azithromycin, widely used in recent years, can change the airway microbiota in patients with chronic lung diseases. Little data exists regarding the effects of azithromycin administration on airway microbiota among healthy adults. Therefore, we conducted a randomized, double-blind, placebo-controlled trial to assess the process of variation and re-establishment of the airway microbiota after azithromycin exposure in healthy adults. Methods: Forty-eight healthy volunteers were enrolled and randomly assigned into two groups. 500mg azithromycin or placebo was administered once daily for 3 days. We collected the induced sputum at the day before the drugs administration (D0), the day after the treatment course was completed (D4), 14 days, 30 days and 60 days post-dosing. 16S rRNA gene sequencing and quantification were applied to the induced sputum samples. We collected the environmental information including air quality data [particulate matter (PM 2.5 ) and PM 10 , air quality index (AQI) values] that might have an influence on the airway microbiota during the study. The subjects’ respiratory tract infection (RTI) events during sampling were recorded. Results: Azithromycin didn’t alter bacterial load but significantly reduced species richness and Shannon index. Azithromycin exposure resulted in decrease in the detection rate and relative abundance of different families belonging to Veillonellaceae , Pasteurellaceae , Leptotrichiaceae , Neisseriaceae and Fusobacteriaceae . By contrast, the relative abundance of taxa belonging to Streptococcus increased immediately after azithromycin intervention. The shifts in the microbial community composition require about 14 days to recover while alpha-diversity recovered later. The high concentration of PM 2.5 contributed to a novel variability in microbial community composition of azithromycin group at D30 (30 days after baseline). The network analysis found that azithromycin altered the microbial interactions within airway microbiota. The influence was still obvious at D14 when the relative abundance of most taxa had returned to the baseline level. Conclusions: Azithromycin has transient effect in airway microbiota of healthy adults and decreases the ability of the airway microbiota resilient from PM 2.5 stress. The influence of azithromycin on microbial interactions is noteworthy though the airway microbiota has returned to the near-baseline level.Registration: Chinese Clinical Trial Registry (ChiCTR1800018494), September, 2018. http://www.chictr.org.cn/edit.aspx?pid=31269&htm=4

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